THE PARADOXICAL EFFECT OF TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) IN ENDOTOXIN-INDUCED UVEITIS

Purpose. To investigate the role of TNF-alpha in endotoxin-induced uve itis (EIU) in mice. Methods. To neutralize TNF-alpha activity, mice we re pretreated with either repeated injections of this cytokine or a si ngle injection of antibody against it. The mice were then injected int raperitoneally with 500 mug endotoxin, to induce lethal septic shock, or into the footpad with 200 mug to induce EIU. Results. Although both pretreatments conferred protection against the systemic toxic effects of LPS, TNF-resistant mice and mice treated with anti-TNF-alpha antib ody demonstrated an exacerbation of EIU when compared to control anima ls. Conclusion. Unlike its apparent participation in the systemic effe ct of endotoxin, TNF-alpha is not directly involved in the pathogenesi s of EIU and may even protect against the inflammatory processes of th is disease.